The purposes of this research are: 1) the development of laboratory procedures for the evaluation of the abuse potential of a variety of drugs including psychomotor stimulants, 2) to analyze the efficacy of pharmacological and behavioral manipulations in the reduction or elimination of the self-administration of abused drugs, including psychomotor stimulants and opiates, 3) to gain insights into the behavioral and biochemical mechanisms underlying the reinforcing actions of drugs. Rhesus monkeys conditioned to lever press for intravenous drug reinforcers will serve as models for human drug users. Evaluation of abuse potential will include a drug escape-avoidance procedure and a multiple schedule procedure now being validated as well as the established substitution, 23-hr access, and choice procedures previously developed in our laboratory. Reduction of self-administration will be approached by manipulation of behavioral and pharmacological/immunological variables. Behavior will be modified by punishment such as electric shock, and by introduction of such alternate reinforcers as food, water, and visual access to other monkeys. Experiments are in progress using narcotic antagonists and specific antibody to reduce opiate self-administration. The effects of pharmacological agents such as AMPT and phenothiazines on psychomotor stimulant self-administration will also be investigated. Changes in self-administration due to structural modification of the drug reinforcers themselves are being explored in experiments with a series of N-alkyl amphetamines.